The autophagy-lysosomal system comprises a highly dynamic and interconnected vesicular network that plays a central role in maintaining proteostasis and cellular homeostasis. In this study, we uncovered the deubiquitinating enzyme (DUB), dUsp45/USP45, as a key player in regulating autophagy and lysosomal activity in Drosophila and mammalian cells. Loss of dUsp45/USP45 results in autophagy activation and increased levels of V-ATPase to lysosomes, thus enhancing lysosomal acidification and function. Furthermore, we identified the actin-binding protein Coronin 1B (Coro1B) as a substrate of USP45. USP45 interacts with and deubiquitinates Coro1B, thereby stabilizing Coro1B levels. Notably, the ablation of USP45 or Coro1B promotes the formation of F-actin patches and the translocation of V-ATPase to lysosomes in an N-WASP-dependent manner. Additionally, we observed positive effects of dUsp45 depletion on extending lifespan and ameliorating polyglutamine (polyQ)-induced toxicity in Drosophila. Our findings highlight the important role of dUsp45/USP45 in regulating lysosomal function by modulating actin structures through Coro1B.

The specific hybridization states of carbon atoms shape diamond and graphite, two well-known allotropes. Under specific conditions, diamond undergoes graphitization, resulting in distinct microstructural and macroscopic property changes. The graphitization of diamond has emerged as a core technology in many application-driven fields. This paper comprehensively reviewed studies on diamond graphitization across various domains to address urgent demands in these industries and the forthcoming semiconductor revolution. Beginning with the definition of diamond graphitization, the article explored its manifestations, thermodynamic and kinetic mechanisms, and influencing factors. The research on diamond graphitization was divided into three stages, focusing on fields such as heating/heat treatment, diamond tools/coatings, irradiation/ion implantation, dissolution/chemical etching, polishing, and simulation/emulation. The key distinctions between graphitization, amorphization, and oxidation were clarified, and the effects of temperature, pressure, atmosphere, and processing parameters on graphitization were summarized. The article introduced the functional application technology from the perspective of utilizing or suppressing diamond graphitization, followed by prospects for future developments in the field of diamond graphitization research.

The quantum anomalous Hall (QAH) effect in two-dimensional (2D) topological materials has attracted widespread attention due to its potential for dissipationless chiral edge transport without an external magnetic field, which is highly promising for low-power electronic applications. However, identifying materials that exhibit these properties remains particularly challenging, as only a limited number of such materials are known, raising the intriguing question of whether it is possible to induce the QAH effect in materials with ordinary properties through structural modifications. In this work, we grow an unreported 2D titanium selenide (Ti3Se4) on a Cu(111) substrate using molecular beam epitaxy. Low-energy electron diffraction and scanning tunneling microscopy characterizations reveal a 7×7 brick-like structure. First-principles calculations and X-ray photoelectron spectroscopy measurements confirm its composition to be Ti3Se4. Our calculations further demonstrate that monolayer Ti3Se4, in its grown form on Cu(111), has the potential to host the QAH effect. Interestingly, when we examine its freestanding form, the monolayer transitions from a QAH insulator candidate into a conventional semiconductor, despite only minor differences in their atomic structures. This transition enlightens us that subtle lattice adjustments can induce a transition from semiconductor to QAH properties in freestanding Ti3Se4. This discovery provides a potential route to engineering practical materials that may exhibit the QAH effect.

Flat-surfaced and large-size diamond wafers are essential for industrial applications, analogous to silicon (Si) wafers over 10-inch. A promising approach for the industrial-scale production of large-size diamond wafers involves chemical vapor deposition (CVD) techniques that generate large-area plasma. This article explores the growing and polishing methods aiming at CVD diamond wafers over 10-inch, based on our previous works and existing literature. The continuous growing strategy is proposed by combining radio frequency induction coupled plasma-enhanced CVD (RFICP CVD) and repositionable (or movable) substrate based on the Van der Drift growth mechanism. Molten iron erosion polishing (MIEP) is considered a method capable of polishing wafers over 10-inch due to its high material removal rate (MRR), size-unlimited, great stress-released, and damage-free characteristics. The proposed methodology lays the foundation for manufacturing flat-surfaced, large-sized diamond wafers for application-oriented purposes.

Surface states of O-terminated diamond determine the electronic properties of devices. The in-situ realization of the surface properties in atomic scale relies on ultra-high vacuum and sophisticated techniques. Here, we propose the utilization of diamond microelectromechanical system (MEMS) to reveal the surface adsorption/desorption of oxygen (O)-terminated diamond. Our strategy is to measure the resonance frequency shift of diamond cantilevers by in-situ heating and cooling the cantilevers. Based on the frequency shift, the mass and thickness of the adsorption layer of O-terminated diamond was disclosed to be 0.0015 pg/mu m(2) and similar to 0.4 nm, providing a new insight into semiconductor electronics.

The ubiquitin-proteasome system (UPS) and macroautophagy/autophagy are two major pathways for maintaining cellular protein homeostasis. Increasing evidence has highlighted the complex interactions and crosstalk between these pathways; however, the specific molecules and mechanisms mediating the interplay between the UPS and autophagy are still not fully elucidated. In this study, we discovered that knocking down the Drosophila Cul2 (Cullin 2)-RING ubiquitin ligase complex adaptor CG12084/DmZer1 impedes autophagy and autophagic flux. DmZer1 interacts with the Drosophila SQSTM1/p62 homolog ref(2)P, promoting its association with ubiquitinated proteins and degradation. ref(2)P is a crucial player in regulating autophagy and the Keap1-cnc/NFE2L2 pathway-mediated antioxidant response. Knockdown of DmZer1 leads to the formation of ref(2)P bodies, which sequester Keap1 and promote cnc/NFE2L2-mediated antioxidant responses under oxidative stress conditions. These findings reveal the pivotal role of DmZer1 in regulating autophagy and the ref(2)P-Keap1-cnc/NFE2L2-mediated oxidative stress response.Abbreviations: ARM: armadillo-like domain; ATG: autophagy related; BTZ: bortezomib; CL1-GFP: GFP fused with a CL1 degron; cnc: cap-n-collar; co-IP: co-immunoprecipitation; CRL2: Cullin 2-RING E3 ubiquitin ligase complex; CQ: chloroquine; CUL2/Cul2: cullin 2; EloB: Elongin B; EloC: Elongin C; esg: escargot; ISCs: intestinal stem cells; KEAP1: kelch like ECH associated protein 1; LIR: LC3-interacting region; LLPS: liquid-liquid phase separation; LRR: leucine-rich repeat; NFE2L2/Nrf2: NFE2 like bZIP transcription factor 2; p-H3: phospho-histone H3; PQ: paraquat; ref(2)P: refractory to sigma P; SQSTM1/p62: sequestosome 1; UBA: ubiquitin-associated; UPS: ubiquitin-proteasome system; VHL: von Hippel-Lindau tumor suppressor; ZER1: zyg-11 related cell cycle regulator.

Diamond holds immense potential for high-power electronics due to its ultrahigh breakdown field strength and exceptional thermal conductivity. However, material failure under extreme electric fields necessitates a fundamental understanding of crystallographic-orientation-dependent breakdown mechanisms. In this work, we designed and performed in situ breakdown experiments on single-crystal diamond within the transmission electron microscopy (TEM) mode, achieving controlled breakdown under real-time observation. Comprehensive structural, compositional, and stress analyses revealed that failure initiates preferentially along the (111) plane, driven by sequential lattice distortion and amorphization. Molecular dynamics (MD) simulations further elucidated atomic-scale degradation pathways, demonstrating anisotropic thermal stability across low-index crystallographic orientations. The (111)-oriented surface exhibited pronounced structural collapse under thermal stress, while (100) and (110) planes maintained integrity until higher thresholds. This work’s integrated experimental-computational approach clarifies crystallographic dependency in diamond breakdown, offering critical insights for designing robust diamond devices.

Aiming at the long-standing difficulties in polishing polycrystalline chemical vapor deposition (CVD) diamond wafers efficiently and safely, a thermo-chemical polishing (TCP) method of molten iron erosion polishing (MIEP) was proposed, thus achieving rapid improvement of the surface roughness (Ra) for polycrystalline diamond wafers. By designing the experimental equipment and parameters, the diamond wafers were immersed in molten iron to be polished. The experimental results of surface roughness measured by white light interferometer showed that the original surface roughness (Ra, -30.850 mu m) was reduced to-5.204 mu m in 10 s of MIEP. Followed by 10 min of mechanical polishing (MP) further polishing, the average Ra was reduced to-14 nm. The material removal rate (MRR) of the MIEP reached 46,800 mu m/h, and the average polishing rate (PR) reached 157.395 mu m/min. The thorough analysis of Raman and X-ray photoelectron spectroscopy (XPS) results revealed the material removal mechanism as the dissolution and the diffusion of carbon atoms into molten iron, which caused the high MRR of this new polishing method.

Macroautophagy/autophagy is a complex degradation process with a dual role in cell death that is influenced by the cell types that are involved and the stressors they are exposed to. Ferroptosis is an iron-dependent oxidative form of cell death characterized by unrestricted lipid peroxidation in the context of heterogeneous and plastic mechanisms. Recent studies have shed light on the involvement of specific types of autophagy (e.g. ferritinophagy, lipophagy, and clockophagy) in initiating or executing ferroptotic cell death through the selective degradation of anti-injury proteins or organelles. Conversely, other forms of selective autophagy (e.g. reticulophagy and lysophagy) enhance the cellular defense against ferroptotic damage. Dysregulated autophagy-dependent ferroptosis has implications for a diverse range of pathological conditions. This review aims to present an updated definition of autophagy-dependent ferroptosis, discuss influential substrates and receptors, outline experimental methods, and propose guidelines for interpreting the results.Abbreviation: 3-MA:3-methyladenine; 4HNE: 4-hydroxynonenal; ACD: accidentalcell death; ADF: autophagy-dependentferroptosis; ARE: antioxidant response element; BH2:dihydrobiopterin; BH4: tetrahydrobiopterin; BMDMs: bonemarrow-derived macrophages; CMA: chaperone-mediated autophagy; CQ:chloroquine; DAMPs: danger/damage-associated molecular patterns; EMT,epithelial-mesenchymal transition; EPR: electronparamagnetic resonance; ER, endoplasmic reticulum; FRET: Försterresonance energy transfer; GFP: green fluorescent protein;GSH: glutathione;IF: immunofluorescence; IHC: immunohistochemistry; IOP, intraocularpressure; IRI: ischemia-reperfusion injury; LAA: linoleamide alkyne;MDA: malondialdehyde; PGSK: Phen Green™ SK;RCD: regulatedcell death; PUFAs: polyunsaturated fatty acids; RFP: red fluorescentprotein;ROS: reactive oxygen species; TBA: thiobarbituricacid; TBARS: thiobarbituric acid reactive substances; TEM:transmission electron microscopy.

T-carbon, as one of new carbon allotropes that was first predicted and then successfully synthesized, has been attracting intensive research interest in recent years and has emerged potential applications in various areas. Here we use the frequency-domain thermoreflectance technique to measure for the first time the thermal conductivity (kappa) of T-carbon, and report the power law behavior of kappa(T) - T-0.75 in T-carbon, with a value of 31.9 Wm- 1K-1 at 300 K, which are nicely consistent with first-principles calculations (33.06 Wm- 1K-1). Among all existing carbon crystals, we find that T-carbon has the lowest thermal conductivity, being nearly 50 times lower than that of cubic diamond, which is caused by the large scattering phase space and strong phonon anharmonicity of C-C bonds with sp3 hybridization in T-carbon. Our study reveals that T-carbon with particularly low thermal conductivity could have potential applications in energy converting devices, and the analyzed mechanism would deepen our understanding on the thermal transport and chemical bonding of carbon crystals.

The ubiquitin-proteasome system (UPS) and autophagy are highly conserved processes that maintain cellular health through the clearance of misfolded/aberrant proteins and damaged organelles. Ubiquitination is a crucial protein modification to regulate entry in these two pathways. However, the function of deubiquitinases (DUBs) in the UPS and autophagy remains largely unclear. The Leon/USP5 deubiquitinase is essential for maintaining ubiquitin homeostasis and proteasome function. In our recent study, we found that Leon/USP5 depletion resulted in the induction of autophagosome formation and an enhancement of the autophagic flux. Additionally, a genetic analysis in Drosophila revealed that Leon overexpression suppressed Atg1-induced cell death. We further showed that Leon/USP5 interacts with the autophagy initiator Atg1/ULK1, regulating its levels and thus modulating autophagosome formation. These findings suggest that Leon/USP5 plays a dual role in regulation of UPS and autophagy. Abbreviations: Atg1: autophagy-related 1; Atg7: autophagy-related 7; DUB: deubiquitinase; ED: enzyme dead; PTM: post-translational modification; SQSTM1: sequestosome 1; ULK1: unc-51 like autophagy activating kinase 1; UPS: ubiquitin-proteasome system; USP5: ubiquitin-specific proteinase 5; WT: wild-type.

Accumulating evidence has shown that the quality of proteins must be tightly monitored and controlled to maintain cellular proteostasis. Misfolded proteins and protein aggregates are targeted for degradation through the ubiquitin proteasome (UPS) and autophagy-lysosome systems. The ubiquitination and deubiquitinating enzymes (DUBs) have been reported to play pivotal roles in the regulation of the UPS system. However, the function of DUBs in the regulation of autophagy remain to be elucidated. In this study, we found that knockdown of Leon/USP5 caused a marked increase in the formation of autophagosomes and autophagic flux under well-fed conditions. Genetic analysis revealed that overexpression of Leon suppressed Atg1-induced cell death in Drosophila. Immunoblotting assays further showed a strong interaction between Leon/USP5 and the autophagy initiating kinase Atg1/ULK1. Depletion of Leon/USP5 led to increased levels of Atg1/ULK1. Our findings indicate that Leon/USP5 is an autophagic DUB that interacts with Atg1/ULK1, negatively regulating the autophagic process.

Stable-operation in the high-temperature regimes (300°C~500°C) for the current magnetic sensors has the thermal-reliability problem. In this work, we propose and demonstrate an on-chip single-crystal diamond (SCD) MEMS magnetic sensor able to work at 500°C by integrating a magnetostrictive FeGa film on a SCD cantilever. The SCD MEMS magnetic sensor exhibits a high thermal-stability operation up to 500°C, showing a magnetic sensitivity of 2.8 Hz/mT at 25°C, 7.5 Hz/mT at 300°C, and 17.7 Hz/mT at 500°C, respectively. The concept of a SCD resonator functionalized with a magnetostrictive film offers a promising strategy to develop high-temperature magnetic sensors with high thermal-reliability.

Protein tyrosine phosphatase: phospho-protein complex structure determination, which requires to understand how specificity is achieved at the protein level remains a significant challenge for protein crystallography and cryoEM due to the transient nature of binding interactions. Using rPTPεD1 and phospho-SrcKD as a model system, we established an integrative workflow involving protein crystallography, SAXS and pTyr-tailored MD simulations to reveal the complex formed between rPTPεD1 and phospho-SrcKD, revealing transient protein–protein interactions distal to the active site. To support our finding, we determined the associate rate between rPTPεD1 and phospho-SrcKD and showed that a single mutation on rPTPεD1 disrupts this transient interaction, resulting in the reduction of association rate and activity. Our simulations suggest that rPTPεD1 employs a binding mechanism involving conformational change prior to the engagement of cSrcKD. This integrative approach is applicable to other PTP: phospho-protein complex determination and is a general approach for elucidating transient protein surface interactions.

In response to ionizing radiation (IR), stem cells undergo cell cycle arrest, senescence, premature differentiation, or cell death. The decision between survival and death is critical during tumorigenesis and effective killing of cancer cells. We used the larval Drosophila lymph gland, a hematopoietic organ, as a model to understand the mechanism for cell fate decisions during stem cell development. The hematopoietic progenitors survived or died via apoptosis when larvae were irradiated in early or late third instar larval (L3) stages, respectively. In late L3 progenitors, the basal level of polo ( Drosophila PLK1) was low, enabling IR-induced activation of lok ( Drosophila CHK2), which was necessary and sufficient for inducing autophagy and reactive oxygen species (ROS) production resulting in cell death. The high level of polo in early L3 progenitors negatively regulated lok resulting in significantly low or undetectable levels of ROS or autophagy, respectively. The surviving early L3 progenitors underwent cell cycle arrest followed by premature differentiation affected by tefu ( Drosophila ATM) and lok mutation. These results provide clues for designing effective therapeutic strategies for cancer.Summary statement We elucidated the mechanism underlying cell fate decisions during stem cell development in larval Drosophila , which will help develop effective cancer treatment modalities.### Competing Interest StatementThe authors have declared no competing interest.

The mainstream polishing methods were reviewed in light of polycrystalline CVD diamond wafer with large area. The principles, equipment, and processes of the mainstream polishing methods were reviewed, and the processing characteristics of these methods were compared. The material removal rate (MRR), polishing rate (PR), and minimum surface roughness (Ra) obtained by each polishing method were summed up. The non-contact method has a relatively higher MRR than the contact method, while the contact method has a relatively smaller final roughness than the non-contact method. Two factors, K (K = ΔRa/Δm, ΔRa is the reduction of the surface roughness, Δm is the mass loss) and CI (CI = K/t, t is the total polishing time), were proposed to evaluate the influence of the polishing parameters on the polishing course in the contact polishing methods and to describe the feature of each polishing method, respectively. The variation of the K value indicated that the polishing load and the polishing plate speed did not always influence the polishing effect monotonically in every contact polishing method, and it should be optimized to obtain fine surface roughness with the tiny mass loss. The CI value showed that the non-contact polishing method possessed the feature of high roughness improvement with low mass loss in the unit polishing time. These results reveal how to move forward on the path to polishing large area polycrystalline CVD diamond wafer.

Excessive generation and accumulation of highly reactive oxidizing molecules causes oxidative stress and oxidative damage to cellular components. Accumulating evidence indicates that autophagy diminishes oxidative damage in cells and maintains redox homeostasis by degrading and recycling intracellular damaged components. Here, we show that TRAF6 E3 ubiquitin ligase and A20 deubiquitinase coordinate to regulate ATG9A ubiquitination and autophagy activation in cells responding to oxidative stress. The ROS-dependent TRAF6-mediated non-proteolytic, K48/63-linked ubiquitination of ATG9A enhances its association with Beclin 1 and the assembly of VPS34-UVRAG complex, thereby stimulating autophagy. Notably, expression of the ATG9A ubiquitination mutants impairs ROS-induced VPS34 activation and autophagy. We further find that lipopolysaccharide (LPS)-induced ROS production also stimulates TRAF6-mediated ATG9A ubiquitination. Ablation of ATG9A causes aberrant TLR4 endosomal trafficking and decreases IRF-3 phosphorylation in LPS-stimulated macrophages. Our findings provide important insights into how K48/K63-linked ubiquitination of ATG9A contributes to the regulation of oxidative stress-induced autophagy.

Autophagy regulates cellular homeostasis by degrading and recycling cytosolic components and damaged organelles. Disruption of autophagic flux has been shown to induce or facilitate neurodegeneration and accumulation of autophagic vesicles is overt in neurodegenerative diseases. The fruit fly Drosophila has been used as a model system to identify new factors that regulate physiology and disease. Here we provide a historical perspective of how the fly models have offered mechanistic evidence to understand the role of autophagy in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Charcot-Marie-Tooth neuropathy, and polyglutamine disorders. Autophagy also plays a pivotal role in maintaining tissue homeostasis and protecting organism health. The gastrointestinal tract regulates organism health by modulating food intake, energy balance, and immunity. Growing evidence is strengthening the link between autophagy and digestive tract health in recent years. Here, we also discuss how the fly models have advanced the understanding of digestive physiology regulated by autophagy.

High levels of reactive oxygen species (ROS) result in oxidative stress, which damages cells and leads to the development of many diseases. Macroautophagy/autophagy plays an important role in protecting cells from diverse stress stimuli including oxidative stress. However, the molecular mechanisms of autophagy activation in response to oxidative stress remain largely unclear. In this study, we showed that TRAF6 mediates oxidative stress-induced ATG9A ubiquitination at two C-terminal lysine residues (K581 and K838). ATG9A ubiquitination promotes its association with BECN1, BECN1-PIK3C3/VPS34-UVRAG complex assembly and PIK3C3/VPS34 activation, thereby activating autophagy and endocytic trafficking. We also identified TNFAIP3/A20 as a negative regulator of oxidative-induced autophagy by counteracting TRAF6-mediated ATG9A ubiquitination. Moreover, ATG9A depletion attenuates LPS-induced autophagy and causes aberrant TLR4 signaling and inflammatory responses. Our findings revealed a critical role of ATG9A ubiquitination in oxidative stress-induced autophagy, endocytic trafficking and innate immunity.

本文对CVD（Chemical Vapour Deposition, CVD）外延生长中作为衬底的高温高压（HTHP）单晶金刚石进行拉曼光谱测试,利用谱峰半高宽（FWHM）判断了衬底的结晶质量。开展了升温（室温～1 000℃）和降温（1 000℃～室温）过程中衬底晶格变化的X射线原位测量研究。实验表明:衬底的晶格常数随温度变化而变化,在1 000℃时因晶格变化而产生的应力大小为GPa量级。晶格常数在降温过程要比升温过程的数值大,线膨胀系数的计算结果也发现了相同的现象。根据傅里叶红外光谱仪（FT-IR）测试结果推断:造成上述变温过程中晶格变化差异的原因在于样品中氮浓度的不同,其中氮浓度越高,拉曼光谱的半高宽越大,衬底的晶格常数变化越大,线膨胀系数越大。